The UC San Diego (UCSD) Moores Cancer Center (MCC) has a rich history as a matrix, NCI-designated comprehensive cancer center, now with 239 members from 28 UCSD departments. Peer-reviewed MCC funding is $118.3 million (directcosts), of which $33.2 million is from the NCI. An additional $15.6 million from non-peer-reviewed sources results in total direct-cost funding of $133.9 million. We have published over 4000 cancer-focused papers in the funding period (20% inter- or intraprogrammatic; 10% in journals with an impact factor >15). MCC is surrounded by several other major life-science research institutes and 489 biotechnology companies in San Diego/La Jolla, the 2nd largest life-sciences cluster in the US. MCC is the only NCI-designated comprehensive cancer center in this region. MCC leverages this advantage to save lives by transforming cancer prevention, detection, and care (mission) and to make personalized cancer medicine a reality (vision). This is our first renewal application as a consortium center with partner San Diego State University (SDSU), thus formalizing long-standing, productive collaborations between MCC and SDSU. As designed, the MCC building 1) stimulates interdisciplinary collaboration between physicians and scientists in the Center's Divisions of Basic Science, Clinical Science, and Population Science, 2) assembles the extensive NCI-supported Shared Resources in a common, accessible site, and 3) acts as an academia-industry hub for translational cancer researchers within the public and private sectors of San Diego. The vast majority of members are in the MCC building or on the UCSD campus; others are in nearby La Jolla institutes. This application reports on six Research Programs: Cancer Biology and Signaling, Cancer Genomes and Networks, Hematologic Malignancies, Solid Tumor Therapeutics, Cancer Prevention, and Reducing Cancer Disparities. We also propose seven Shared Resources: Biorepository and Tissue Technology, Biostatistics, Genomics and Bioinformatics, Microscopy, Flow Cytometry, Transgenic Mouse, Diet and Physical Activity. All Programs and Resources reflect the scientific strengths and goals of the MCC. MCC is poised to leverage its exceptional basic and population sciences and San Diego-wide collaborations (academic and private-sector) in developing innovative science-based cancer prevention and treatment. This application summarizes our investments, recruitments, collaborations, organizational changes, plans, and progress toward this goal.